Nanostructured Luminescent Micelles: Efficient “Functional Materials” for Sensing Nitroaromatic and Nitramine Explosives

Luminescent micelles are extensively studied molecular scaffolds used in applied supramolecular chemistry. These are particularly important due to their uniquely organized supramolecular structure and chemically responsive physical and optical features. Various luminescent tags can be incorporated with these amphiphilic micelles to create efficient luminescent probes that can be utilized as “chemical noses” (sensors) for toxic and hazardous materials, bioimaging, drug delivery and transport, etc. Due to their amphiphilic nature and well-defined reorganized self-assembled geometry, these nano-constructs are desirable candidates for size and shape complementary guest binding or sensing a specific analyte. A large number of articles describing micellar fluorogenic probes are reported, which are used for cation/anion sensing, amino acid and protein sensing, drug delivery, and chemo-sensing. However, this particular review article critically summarizes the sensing application of nitroaromatic (e.g., trinitrotoluene (TNT), trinitrobenzene (TNB), trinitrophenol (TNP), dinitrobenzene (DNB), etc.) and nitramine explosives (e.g., 1,3,5-trinitro-1,3,5-triazinane, trivially named as “research department explosive” (RDX), 1,3,5,7-tetranitro-1,3,5,7-tetrazocane, commonly known as “high melting explosive” (HMX) etc.). A deeper understanding on these self-assembled luminescent “functional materials” and the physicochemical behavior in the presence of explosive analytes might be helpful to design the next generation of smart nanomaterials for forensic applications. This review article will also provide a “state-of-the-art” coverage of research involving micellar–explosive adducts demonstrating the intermolecular charge/electron transfer (CT/ET) process operating within the host–guest systems.

8 Sydnone-Based Cycloadditions in Click Chemistry

The 1,3-dipolar cycloaddition of sydnones (1,2,3-oxadiazolium-5-olates) with dipolarophiles, such as alkynes, has recently emerged as a versatile click reaction, with applications ranging from the mild and regioselective preparation of polysubstituted pyrazoles for drug discovery to the metal-free bioorthogonal ligation of biomacromolecules in living cells. This chapter reviews the importance of metal catalysis for controlling the regioselectivity of the copper-mediated reaction (CuSAC), as well as the development of fluorogenic probes, the click and release strategy, and photo-triggered ligations based on strain-promoted sydnone–alkyne cycloadditions (SPSAC).

Squaraine-Based Optical Sensors: Designer Toolbox for Exploring Ionic and Molecular Recognitions

Small molecule-based chromogenic and fluorogenic probes play an indispensable role in many sensing applications. Ideal optical chemosensors should provide selectivity and sensitivity towards a variety of analytes. Synthetic accessibility and attractive photophysical properties have made squaraine dyes an enticing platform for the development of chemosensors. This review highlights the versatility of modular assemblies of squaraine-based chemosensors and chemodosimeters that take advantage of the availability of various structurally and functionally diverse recognition motifs, as well as utilizing additional recognition capabilities due to the unique structural features of the squaraine ring.

Reaction-based fluorogenic probes for selective detection of cysteinyl oxidation in living cells

Measuring reactive oxygen, nitrogen and sulfur species in cells is established technology, but turn-on fluorescence tools for detecting the products of their reaction with protein cysteines remain essentially unknown. Toward this goal, here we describe fluorogenic probes for sulfenic acid, a redox modification of protein cysteines inextricably linked to signaling and oxidative stress. The probes, called CysOx1 and CysOx2, are reaction-based, exhibit excellent cell permeability, rapid reactivity, and high selectivity with minimal cytotoxicity. We applied CysOx2 in a cell-based 96-well plate assay to determine whether kinase inhibitors modulate protein S-sulfenylation as well as O-phosphorylation. Analysis of these data revealed an unexpected positive association of S-sulfenylation and inhibition of select kinases within the TK, AGC, and CMGC families including GSK3, a multitasking Ser/Thr kinase and emerging therapeutic target for neurodegenerative and mood disorders. Chemoproteomic mapping of sulfenic acid-modified cysteines in GSK3 inhibitor-treated cells shows that sites of S-oxidation localize to regulatory cysteines within key components of antioxidant defense systems. Our studies with CysOx probes offer up new insights into kinase-inhibitor dependent modulation of sulfenylome dynamics and should accelerate future efforts in the modern era of translational redox medicine.

Chemodivergent manganese-catalyzed C–H activation: modular synthesis of fluorogenic probes

Bioorthogonal late-stage diversification of amino acids and peptides bears enormous potential for drug discovery and molecular imaging. Despite major accomplishments, these strategies largely rely on traditional, lengthy prefunctionalization methods, heavily involving precious transition-metal catalysis. Herein, we report on a resource-economical manganese(I)-catalyzed C–H fluorescent labeling of structurally complex peptides ensured by direct alkynylation and alkenylation manifolds. This modular strategy sets the stage for unraveling structure-activity relationships between structurally discrete fluorophores towards the rational design of BODIPY fluorogenic probes for real-time analysis of immune cell function.